Azithromycin Tablets
DEFINITION
Azithromycin Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of azithromycin (C38H72N2O12).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Solution A:
A solution containing 4.4 mg/mL of dibasic potassium phosphate and 0.5 mg/mL of sodium 1-octanesulfonate. Adjust with phosphoric acid to a pH of 8.20 ± 0.05.
Mobile phase:
Acetonitrile, methanol, and Solution A (9:3:8)
Solution B:
1.7 mg/mL of monobasic ammonium phosphate. Adjust with ammonium hydroxide to a pH of 10.00 ± 0.05.
Diluent A:
Methanol, acetonitrile, and Solution B (7:6:7)
Standard solution:
Dissolve USP Azithromycin RS in Diluent A using about 75% of the final volume, sonicate to dissolve, dilute with Diluent A to volume, and mix to obtain a solution having a known concentration of 0.4 mg/mL of azithromycin.
System suitability stock solution:
0.2 mg/mL of USP Azaerythromycin A RS in acetonitrile. [Note—Sonicate if necessary to dissolve. ]
System suitability solution:
0.02 mg/mL of azaerythromycin A from the System suitability stock solution and 0.02 mg/mL of azithromycin from the Standard solution in Diluent A
Sample stock solution:
Weigh and finely powder NLT 20 Tablets. Transfer an equivalent to 667 mg of azithromycin to a 200-mL volumetric flask. Add 75 mL of Diluent A, and sonicate for NLT 15 min. Shake by mechanical means for NLT 15 min. Allow the solution to equilibrate to room temperature, dilute with Diluent A to volume, and mix.
Sample solution:
0.4 mg/mL of azithromycin from the Sample stock solution in Diluent A. Pass through a filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
50
Flow rate:
1.5 mL/min
Injection size:
50 µL
System suitability
Samples:
Standard solution and System suitability solution
[Note—Identify the peaks by their relative retention times, which are 0.64 and 1.0 for azaerythromycin A and azithromycin, respectively. ]
Suitability requirements
Resolution:
NLT 2.5 between azaerythromycin A and azithromycin, System suitability solution
Column efficiency:
NLT 1000 theoretical plates, Standard solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C38H72N2O12 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × P × F × 100
| rU | = | = peak response of azithromycin from the Sample solution |
| rS | = | = peak response of azithromycin from the Standard solution |
| CS | = | = concentration of USP Azithromycin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of azithromycin in the Sample solution (mg/mL) |
| P | = | = potency of USP Azithromycin RS (µg/mg) |
| F | = | = unit conversion factor, 0.001 mg/µg |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
pH 6.0 phosphate buffer; 900 mL
Apparatus 2:
75 rpm
Time:
30 min
Solution A and Mobile phase:
Proceed as directed in the Assay.
Diluent:
17.5 mg/mL of dibasic potassium phosphate. Adjust with phosphoric acid to a pH of 8.00 ± 0.05. Prepare a mixture of this solution and acetonitrile (80:20).
Standard stock solution:
Dissolve USP Azithromycin RS in Medium to obtain a solution having a known concentration of about (L/1000) mg/mL, where L is the Tablet label claim, in mg.
Standard solution:
Dilute the Standard stock solution with Diluent to obtain a solution having a known concentration of about (L/2000) mg/mL, where L is the Tablet label claim, in mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute a portion of the filtrate with Diluent to obtain a solution having a theoretical concentration of about (L/2000) mg/mL, where L is the Tablet label claim, in mg, assuming complete dissolution.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
50
Flow rate:
1.5 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements:
Column efficiency:
NLT 1000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Determine the amount of C38H72N2O12 dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response of azithromycin from the Sample solution |
| rS | = | = peak response of azithromycin from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = Tablet label claim (mg) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of C38H72N2O12 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
[Note—Use low-actinic glassware. Refrigerate the Standard solution and the Sample solution after preparation and during analysis, using a refrigerated autosampler set at 4. The solutions must be analyzed within 24 h of preparation. ]
. The solutions must be analyzed within 24 h of preparation. ]
Solution B, Diluent A, and System suitability solution:
Proceed as directed in the Assay.
Solution C:
1.8 mg/mL of dibasic sodium phosphate in water
Solution D:
Acetonitrile and methanol (3:1)
Mobile phase:
See the gradient table below.
| Time (min) |
Solution C (%) |
Solution D (%) |
|---|---|---|
| 0 | 50 | 50 |
| 25 | 50 | 50 |
| 30 | 45 | 55 |
| 40 | 40 | 60 |
| 55 | 35 | 65 |
| 60 | 35 | 65 |
| 61 | 50 | 50 |
| 70 | 50 | 50 |
Diluent B:
Methanol and Solution B (1:1)
Blank:
Use Diluent A.
Standard stock solution:
Use the Standard solution as directed in the Assay.
Standard solution:
0.02 mg/mL of azithromycin from the Standard stock solution in Diluent A
Sensitivity solution:
0.004 mg/mL of azithromycin from the Standard solution in Diluent A
Sample stock solution:
Weigh and finely powder NLT 20 Tablets. Transfer an equivalent to 1335 mg of azithromycin to a 100-mL volumetric flask. Add 75 mL of acetonitrile, and sonicate for NLT 15 min. Shake by mechanical means for NLT 15 min. Allow the solution to equilibrate to room temperature, dilute with acetonitrile to volume, and mix.
Sample solution:
Centrifuge an aliquot of the Sample stock solution for 15 min. Transfer 3.0 mL of the supernatant to a 10-mL volumetric flask, dilute with Diluent B to volume, and mix to obtain a solution having a nominal concentration of about 4 mg/mL of azithromycin. Pass through a filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
60
Flow rate:
0.8 mL/min
Autosampler temperature:
4
Injection size:
100 µL
System suitability
Samples:
System suitability solution, Standard solution, and Sensitivity solution
Suitability requirements
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Resolution:
NLT 2.5 between azaerythromycin A and azithromycin, System suitability solution
Relative standard deviation:
NMT 10.0%, Standard solution
Analysis
Samples:
Blank and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × P × F1 × (1/F2) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of azithromycin from the Standard solution |
| CS | = | = concentration of USP Azithromycin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of azithromycin in the Sample solution (mg/mL) |
| P | = | = potency of USP Azithromycin RS (µg/mg) |
| F1 | = | = unit conversion factor, 0.001 mg/µg |
| F2 | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
[Note—The reporting level for impurities is 0.1%. Disregard any peaks in the Sample solution that correspond to peaks in the Blank. ]
Individual impurities:
See Impurity Table 1.
Total impurities:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Azithromycin 3¢-N-oxide | 0.28 | 0.45 | 1.0 |
| 3¢-(N,N-Didemethyl)-3¢-N-formylazithromycin | 0.38 | 1.9 | 1.0 |
| 3¢-(N,N-Didemethyl) azithromycin (aminoazithromycin) |
0.40 | 0.52 | 0.5 |
| Desosaminylazithromycin | 0.47 | 1.1 | 0.5 |
| Azithromycin related compound Fa | 0.53 | 4.8 | 1.0 |
| 3¢-N-Demethylazithromycin | 0.57 | 0.53 | 0.7 |
| 3¢-De(dimethylamino)-3¢-oxoazithromycin | 0.78 | 1.6 | 1.0 |
| 6-Demethylazithromycin (azaerythromycin A)b | 0.82 | — | — |
| Azithromycin | 1.0 | — | — |
| 3-Deoxyazithromycin (azithromycin B)b | 1.3 | — | — |
| 3¢-N-Demethyl-3¢-N-[(4-methylphenyl)sulfonyl] azithromycinb |
1.4 | — | — |
| Any other unspecified impurity | — | 1.0 | 0.2 |
| Total impuritiesb | — | — | 5.0 |
|
a
3¢-(N-Demethyl)-3¢-N-formylazithromycin.
b
These compounds are synthetic process impurities of azithromycin. They are controlled in the drug substance and are listed here for information only. The total impurities specification does not include these impurities.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store at controlled room temperature.
') + '&img=../../images/v35300/c11rs95.gif',600,500);)
') + '&img=../../images/v35300/cas-83905-01-5.gif',600,500);)
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ahalya Wise, M.S.
Senior Scientific Liaison 1-301-816-8161 |
(SM12010) Monographs - Small Molecules 1 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2287
Pharmacopeial Forum: Volume No. 34(5) Page 1143